Novel senescence associated gene, YPEL3, is repressed by estrogen in ER+ mammary tumor cells and required for tamoxifen-induced cellular senescence

Estrogen signaling plays an important role in breast carcinogenesis. An increased understanding of estrogen gene targets and their effects will allow for more directed and effective therapies for individuals with breast cancer, particularly those with estrogen receptor positive tumors resistant to t...

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Bibliographic Details
Published in:International journal of cancer 2012-05, Vol.130 (10), p.2291-2299
Main Authors: Tuttle, Rebecca, Miller, Kelly R., Maiorano, J. Nicholas, Termuhlen, Paula M., Gao, Yongping, Berberich, Steven J.
Format: Article
Language:English
Subjects:
Antineoplastic Agents, Hormonal - pharmacology
Biological and medical sciences
Breast cancer
Breast Neoplasms - genetics
Cancer
Cell Line, Tumor
cellular senescence
Cellular Senescence - drug effects
estrogen receptor
Estrogens
Female
Gene Expression Regulation, Neoplastic - drug effects
Humans
Medical research
Medical sciences
Neoplasms, Hormone-Dependent
p53
Receptors, Estrogen - metabolism
Senescence
tamoxifen
Tamoxifen - pharmacology
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
Tumors
YPEL3
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Summary:Estrogen signaling plays an important role in breast carcinogenesis. An increased understanding of estrogen gene targets and their effects will allow for more directed and effective therapies for individuals with breast cancer, particularly those with estrogen receptor positive tumors resistant to tamoxifen therapy. Here, we identify YPEL3 as a growth suppressive protein downregulated by estrogen in estrogen receptor positive breast cancer cell lines. Estrogen repression of YPEL3 expression was found to be independent of p53 but dependent on estrogen receptor alpha expression. Importantly, YPEL3 expression, which is induced by the removal of estrogen or treatment with tamoxifen triggers cellular senescence in MCF‐7 cells while loss of YPEL3 increases the growth rate of MCF‐7 cells. Taken together these findings suggest that YPEL3 may represent a potential target for directed hormonal therapy for estrogen receptor positive breast cancer patients.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.26239